JPS5813525B2 - anticoccidial agent - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to an anticoccidial agent for animals containing 4-carbamoyl-2-nitropyridine represented by the formula or an acid addition salt thereof as an active ingredient.

Acid addition salts include pharmaceutical non-toxic salts of organic or inorganic acids, such as hydrochloric acid, sulfuric acid, nitric acid, oxalic acid, maleic acid, tartaric acid, malonic acid, citric acid, phthalic acid, naphthalene disulfonic acid salts, etc. can give.

Coccidiosis is a disease caused by coccidia of the protozoan Sporozoa.
It is a parasitic protozoan disease belonging to the order Coccidiformes (order), and is an infectious disease that causes fire extinguisher diseases and malnutrition in poultry and livestock, causing death.It is most common in chickens, but it is most common in domestic rabbits, goats,
It also damages sheep, cattle, ducks, quail, and turkeys, causing great damage to the poultry and livestock industries.

The family Eimeridae of coccidia includes Eimeria and Isospora.
There are more than 10 genera such as Eimeria (Eimeria), but coccidiosis in poultry and livestock is often caused by the genus Eimeria.

Coccidian oocyst (Occyst, protocyte)
is excreted with feces, and under appropriate conditions, after 24 to 48 hours, it forms spores, becomes infectious, and infects orally.

Oocysts initially reproduce asexually within the mucosal cells of the host's cecum or small intestine, during which time they develop the most severe symptoms, and then sexually reproduce to form oocysts, which are excreted with feces. This makes it extremely contagious.

Many preventive treatments using chemotherapeutic agents have been proposed for such coccidiosis in poultry and domestic animals. In particular, as preventive treatments for coccidiosis, for example, sulfa drugs, arsenic compounds, nitrofuran derivatives, nitrophenides, nicarpazin, pyrimidine, etc. Derivatives (antithiamine drugs), quinoline derivatives, guanidine derivatives, antibiotics, etc. have been introduced, but each has its own drawbacks such as efficacy, antiprotozoal spectrum, safety for target animals, and ease of developing drug resistance, so it is unclear which drugs are satisfactory. I can't say that.

The preventive and therapeutic agent for coccidiosis of the present invention is effective against the entire genus Eimeria, and is particularly effective against Ei-meria tenella, the most pathogenic cecal parasite.
ella).

Furthermore, the active ingredient of the present invention is highly effective against strains resistant to thiamine-based anticoccidial agents that are currently widely used.

4-Carbamoyl-2-nitropyridine used in the present invention is a new compound, and as shown in the following formula, the compound (■
) [described in Australian Journal of Chemistry, Vol. 2, 4, p.・American Chemical Society (J.Am.Chem)
．． Soc. )7 Volume 6, page 3167 (1954)
[description] with thionyl chloride to form an acid chloride, and then contacting it with ammonia, or the compound (
(2)) is reacted with a chloroformate (R is an alkyl group, benzyl group or fuunyl group) to form an acid anhydride, and then the acid anhydride is brought into contact with ammonia.

After the reaction, the desired product is obtained by a conventional method.

For example, after the reaction, the crystals are filtered and recrystallized to obtain the desired target product.

Next, the above method will be explained in more detail by referring to a reference example.

Reference example 4-methoxycarbonyl-2-nitropyridine 400m
Stir g with 2 ml of 28% aqueous ammonia at room temperature for 1 hour.

After distilling off the solvent, recrystallization was performed from ethanol-ether to obtain 348 mg of the desired target product.

Melting point (decomposition) 173°C Elemental analysis value Calculated value as C6H5N303: C, 43.12; 3.02;N. 25.1
5 Experimental value: C, 43.17; H. 3.05; N, 25.
04 In carrying out the present invention, 4-carbamoyl-2-nitropyridine or its organic or inorganic acid salts are used in combination with a physiologically harmless carrier, if necessary.

It is usually added to animal feed or dispersed or dissolved in drinking water.

Examples of animal feed include flour, hulls, fermentation residues, lees, and bran.

This sample may be mixed with crushed limestone, talc powder, etc., and the mixture is made into a solid or semi-solid by methods such as crushing, stirring, and rolling.

The above preparations of the invention may contain other anticoccidial agents such as sulfa drugs such as sulfatalorpyrazine, sulfadimethoxine, sulfaquinoxaline; or thiamine derivatives such as pecrothiamine, amprolium, dimethiarium; quinoline derivatives such as buquinolate, decoquinate, methylbenzokuwait: Folate antagonists such as pyrimethamine, diaperidine; antifolates such as monensin; or other anticoccidial agents such as 3-hydroxy-5-hydroxymethyl-2-methylpyridine;
Clopidol (3,5-dichloro-2,6-dimethyl-
4-pyridinol), lobenzidene, and the like.

The dosage concentration of the anticoccidial agent of the present invention cannot be determined unconditionally depending on the type of poultry or livestock, administration method, administration purpose, symptoms, etc., but for example, when preventing by adding it to feed,
Used at 250ppm, 500-1000p for treatment
Used in pm.

Next, a test example showing the effect of the anti-coccidiosis agent of the present invention will be given.

Test Example Test Materials and Test Methods 1) Test chicks: single crowned white leghorn, male chicks, 14 days old from the start of the experiment (immediately after hatching, day-old chicks were fed a compound feed for young chicks that did not contain an anticoccidial agent until the start of the test) They were fed and kept in isolation.

)2) Test coccidium: Eimeria tenella (Eim
eria tenella) sporulating oocysts.
Infection was carried out by orally inoculating 42,000 eggs per wing directly into the pouch.

3) Test drug: 4-carbamoyl-2-nitropyridine 4) Concentration of test drug added to feed: Add 200p of test drug to commercially available compound feed for young chicks that does not contain anticoccidial agent.
pm was mixed.

5) Test method: The above test chicks were raised in isolation from coccidiosis chickens, their health conditions were observed, and the weights of normal chicks were measured. There was a significant difference in the average weight of each group (risk level 5% level).
The birds were divided into 10 birds/area to avoid any confusion.

Furthermore, two groups were established: an infection-free control and a no-medication and infection-free control.

After division, a certain number of oocysts were inoculated in all plots except for the uninfected and unmedicated control plot, and feed containing the test drug was fed at the same time. Lot) feed was maintained.

6) Judgment: Body weight was measured at fixed times from the start of the test (at the time of administration and infection) to the end (7 days after infection).
The number of oocysts in excreted feces was measured every day up to 7 days.

All surviving chicks were necropsied on the 7th day after infection, and the degree of cecal lesions caused by coccidia was determined using Experimental Parasitology (Exptl. Parasit.) Vol. 28, 30-
Johnson & Co. on page 36 (1970)
Judgment was made using a 5-step scale from 0 to 4 according to the method of Johnson and Reid.

The amount of weight gain from the start of the test to the end of the test is defined as the amount of weight gain.
The average weight gain was divided by the number of birds in each test plot.

The number of oocysts in 1 g of feces excreted on the 6th and 7th days after infection was added for each test section to determine the number of oocysts.

Test results It is shown in Table 1.

The anti-coccidial agent of the present invention was found to be more effective than the control group without infection.

Also, no side effects were observed. When administering drugs,
Among the developmental stages of Coccidina, the first asexual reproductive stage and the second asexual reproductive stage are the most effective.

Claims (1)

[Claims] 1. An anticoccidial agent containing 4-carbamoyl-2-nitropyridine or an acid addition salt thereof as an active ingredient.